Process for the manufacture of pantothenic acid and the salts thereof



-"rcaaaa.luues,le4e v UNITED STATES PATENT OFF PROCESS FOR THE MANUFACTURE F PANTOTHENIC ACID AND THE SALTS THEREOF No Drawing. Application July 14, 1943, Serial'No. 494,725. In Switzerland July 11,1942

2 Claims.

Pantothenic acid was found to be a biologically important substance. It may be manufactured by reacting a,-y-dihydroxy-p,p-dimethyl-butyric which is identical with the natural product, is

obtained. Anyloxidant apt to transform a primary alcohol into the corresponding carboxylic acid may be used for the execution of'the inventions Salts of permanganic acid are especially suitable as oxidants.- By the present process it is possible to oxidise theprilnary hydroxy group in the N-alkyl radical without aflecting other parts oi the molecule; this is all the more surprisin since the unace'tylated a,- -dihydroxya,p-dimethyl-butyric acid (3'-hydroxypropyl) amide also dihydroxy-ap-dimethyl butyric acid- (3' hydroxy-propyl) -amide is stirred into 2000 parts by weight of aqueous sulfuric acid at -20 C., the

in 5000 parts of water is caused to flow into the l acid. solution during about 1 hour.. The per- 'manganate is used up immediately. The temperature is maintained between 15 and C. by

' carbonate at -30.C. While carbon dioxide evolves, the water-soluble calcium salt of pantothenic acidis formed. The filtered solution is evaporated to dryness in vacuo, whereupon the residue is dissolved in 200 parts by volume of absolute alcohol. The calcium salt is precipitated by adding acetic ester; For further puriflcation, the calcium salt may be transformed into the cinchohidine salt by precipitating the'cal-- clum in aqueous solution with the calculated v quantity of oxalic acid, concentrating the pantothenic acid in vacuo in order to free the same from water and adding to the methylalcohoiic, solution thereof the calculated quantity of cinchonidine base. The cinchonidine pantothenate obtained by concentration possesses upon recrystallisaton from methyl-ethyl ketone the properties-described in the literature (Beric'hte der Deutschen Chemischen Gesellschaft," vol. 74. year 1941, p e 218), the melting point being at melting point and opticaiactivity are the same as in the cinchonidine salt prepared from pure pantothenic acid.

Alkali or alkali. earth salts may be obtained from the cinchonidine salt by adding to the aqueous solution of the latter the calculated quane said aqueous sulfuric acid containing parts by weight oi' concentrated sulfuric acid. A solution tity of an alkali or alkaline earth, removing down the aqueous solution to dryness.

' V Example 2 I g 289 parts by weight of "dextro-sn-diacetoxyc,p-dimethyl-butyric acid (3' hydroxypropyl) amide are dissolved in 2000 parts of water, a cooled mixture of 120 parts by weight of sulfuric acid in 500 parts of water is added while stirring and a solution of parts by weight of barium permanganatein 5000 parts of water dribbled j thereto at a temperature of between 15 and 20 contains other oxidisableh drox rou y y g N 25 C. After thepermanganate has been completely m 1 used up, a 10 percent solution of barium hy-V A solution oi. 205 pa'rtsby weight of dextro-a droxide is added at the same temperature while continuing the stirring until the. mixture shows a permanent alkaline reaction to phenolphthalein.

7 tion. Barium ions are separated from the clear of 150 parts by weight of barium permanganate filtrate by means of dilute sulfuric acid added in exactly the quantity needed. The filtered solution is evaporated to dryness in vacuo..- There remains a colorless pantothenicacid of sirupy form. It is taken up in 1000 parts of water and stirred with 55 parts by weight of calcium car-- bonate for 2 hours at 30 C. The foaming, which is rather considerable at the beginning, stops nearly completely after. some time. The solution is filtered and evaporated to dryness in vacuo, whereupon the dry residue is dissolved in 300 parts by volume of absolute alcohol and filtered if necessary. Upon addition 01' dry acetic ester,

' the calcium salt of pantothenic acid precipitates. 7 It is sucked off and dried. The cinchonidine salt I prepared from the calcium salt possesses the same properties as those described in Example 1.

Iclaim: 1. Process for the manufacture of pcntothenic acid and the salts thereof, comprising reacting a substance selected from the group consisting oi dextro-a,- -dihydroxyand dextro-sry-diacetoxy-Ap-dimethylbutyric acid (3' hirdroxypropyl) -amid'e' with a salt of permanganic acid.

2. The process of claim 1 in which the reagent- 7 salt is barium permanganate.

o'rro SCI-INIDER- The precipitate is separated by suction illtraf 

